Amino acids are the building blocks which are widespread in the Nature. Even of the limited number of the genetically-coded α-amino acids the Nature composes practically unlimited number of proteins. The “success” of proteins in sustaining life and regulating biochemical processes prompted chemists over the world to mimic their structure and function in search for new drug candidates – peptidomimetics. It is therefore not surprising that the selection of the natural proteinogenic amino acids was substantially enriched by creating new, unnatural amino acids, specially designed to improve pharmacokinetic and pharmacodynamic properties of the peptidomimetics and other biologically active compounds based on them.
"The α-amino acids, molecules of which have restricted conformational flexibility, are widely used in design of peptidomimetics, peptide models, and in systematic search for biologically active compounds. Among these amino acids, a distinct class of compounds can be highlighted, namely - conformationally rigid amino acids (CRA). Certain torsion angles, which describe the conformation of a polypeptide chain at the CRA, are "fixed" that allows predicting and controlling it to some extent. Many structural studies show that the CRA residues can dictate certain conformation of the peptide chain around them, consequently, they can stabilize or destabilize certain peptide secondary structure elements.
For Palladium-Catalysed C–N And C–C Cross-Couplings.
Air and moisture insensitive auxiliary ligands for highly efficient palladium catalysts. These ultra-low loading (high TONs or TOFs) catalysts have shown excellent activity in Suzuki cross-coupling with aryl bromides and chlorides, Heck vinylation, Heck-Sonogashira alkynylation and allylic amination of allyl acetates (Tsuji–Trost type reactions). Low loadings of the catalysts ensure minimal contamination of the final compounds with palladium and simplify the purification procedures. High stability of the allows to store them for unlimited time without special precautions.
In the last decade, development of new drugs increasingly requires the use of chiral building blocks for hit-to-lead optimization, and even on early stages - in search for efficient hit compounds. The main fundamental reason for this lies in the fact that almost all the biological targets are chiral, and the drug-receptor interaction requires strict match of chirality. The formal reason results from strengthening the regulatory guidance for submitting new drug applications in Europe and USA which concern chirality issues.